Should we care about sativex-induced neurobehavioral effects? A 6-month follow-up study.

OBJECTIVE: Sativex® is an exclusive cannabinoid-based drug approved for the treatment of spasticity due to Multiple Sclerosis (MS). The most common side effects include dizziness, nausea, and somnolence. However, it is still under debate whether the drug could cause negative cognitive effects. The aim of our study was to investigate the effect of Sativex® on functional and psychological status in cannabis-naïve MS patients. PATIENTS AND METHODS: All the study participants (i.e. 40 patients affected by MS) underwent a specific clinical and neuropsychological assessment to investigate spasticity and associated symptoms, besides the cognitive and psychiatric domains commonly impaired in MS, before and after 1 and 6 months of Sativex® administration. RESULTS: After the treatment, we did not observe any significant neurobehavioral impairment in all the patients, but one. CONCLUSIONS: Our findings suggest that Sativex® treatment does not significantly affect the cognitive and neurobehavioral functions. However, the study supports the relevance of an extensive neuropsychological evaluation in MS patients selected for the drug administration, in an attempt to early detect the uncommon but important neurobehavioral side effects.

Severe septal panniculitis in a multiple sclerosis patient treated with interferon-beta.

We report a memorable case of severe septal panniculitis in an MS patient following the subcutaneous administration of interferon beta-1b, manifesting as a painful, indurated, erythematous lesion of the thigh, which appeared at the injection site.

R3 nociceptive reflex in multiple sclerosis patients with paroxysmal symptoms treated with gabapentin.

Gabapentin (GBP) is a new, well-tolerated antiepileptic drug found to be effective for painful paroxysmal symptoms (PS) in multiple sclerosis (MS). The aim of this study was to obtain a neurophysiological evaluation of the effects of GBP on the nociceptive system of MS patients suffering PS. We studied 10 MS patients, 6 males, 4 females (mean age 47.3 years), suffering PS (3 had trigeminal neuralgia, 1 painful tonic spasms and 6 dysesthetic or paresthetic symptoms). Three patients were, at the same time, also being treated with carbamazepine. Pain was evaluated by means of the Visual Faces Scale. R3 nociceptive reflex was recorded after 2 weeks' treatment. R3 thresholds and latencies were evaluated and a statistical analysis was performed. A significant variation was found in R3 thresholds between the values recorded before and during GBP treatment; no significant variation was observed in R3 latencies.

Nociceptive R3 reflex in relapsing-remitting multiple sclerosis patients.

Pain in multiple sclerosis (MS) patients has only recently been recognised as a genuine symptom of this disease. It is important to determine whether this pain is the consequence of another symptom of MS or whether it is due to a demyelinating lesion affecting pain pathways. A close relationship has been found between the R3 component of the blink reflex and the pain threshold. The aim of this work was to carry out an objective evaluation of the nociceptive system in MS patients by means of the R3 component of the blink reflex. The study was performed on 20 healthy volunteers and on 20 clinically defined relapsing-remitting MS patients with EDSS not > 3.5, normal R1 and R2 components of the blink-reflex, personal and family anamnesis negative for migraine and trigeminal neuralgia; the patients were not taking drugs at the time of the test. A significant difference was found, between healthy volunteers and patients, for R3 threshold, pain threshold and R3 latency.

Enhanced spasticity in primary progressive MS patients treated with interferon beta-1b.

Spasticity is a disabling symptom of MS that is enhanced during interferon beta-lb (IFNbeta-1b) treatment. Nineteen patients with primary progressive MS were treated with IFNbeta-1b; an additional 19 patients did not receive this treatment. Thirteen of the 19 patients treated with IFNbeta-1b had increased spasticity requiring increased antispasticity drug administration. This observation suggests that further studies are needed before interferons can be so widely used in primary progressive MS patients.

Epileptic seizure associated with intracerebroventricular and intrathecal morphine bolus.

We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.

Imaging of inner cerebral trauma.

The concept of "Inner cerebral trauma" (ICT) has been preliminary defined as a characteristic topographic pattern of deep brain lesions produced by physical forces occurring within the cranial cavity in closed head injury of the acceleration/deceleration type. The lesions, based on neuropathological examinations, are characteristically localized in the "centro-axial" regions of the brain. The extent of ICT is often underestimated by CT. Due to assess the value of MR imaging, 83 patients with ICT were examined on a 1.5 T unit in different stages after trauma. The pattern of lesions, as shown with MR imaging, correlated well with neuropathological studies, suggesting a multifocal pathogenesis of severe traumatic brain injury.

Intrathecal baclofen application in patients with supraspinal spasticity secondary to severe traumatic brain injury.

Intrathecal application of baclofen is considered the treatment of choice in patients suffering from spinal spasticity insufficiently responding to conventional oral antispastic medication. This approach has also been used successfully in cases with spasticity of supraspinal origin. To achieve a good therapeutic response in the latter condition the amount of intrathecal baclofen has to be approximately twice the dosage required in spinal spasticity. We report on 8 patients suffering from supraspinal spasticity due to severe traumatic brain injury. Intrathecal baclofen reduced spasticity in all patients (mean Ashworth Score from 3.9 to 1.6; mean Reflex Score from 4.0 to 1.4). In some cases improvement of motor performance and in one case recovery of bladder function were noted. In two patients focal epileptic seizures with secondary generalization seemed to be associated with the application of baclofen. The local intrathecal application of baclofen has proven to be an effective therapy in otherwise intractable cases of severe supraspinal spasticity.

Epileptic seizures associated with intrathecal baclofen application.

We report the clinical and EEG findings in three patients presenting with seizures associated with intrathecal baclofen application for treatment of spasticity. All patients had a history of traumatic brain injury, while one patient also suffered a spinal cord injury. Two patients experienced their first seizure following intrathecal baclofen test bolus injection. Another patient had convulsions on two occasions: following postoperative baclofen dose adjustment, and after sleep deprivation. Structural brain disease seems prerequisite for baclofen to exert epileptogenic activity, since seizures have not occurred in patients receiving intrathecal baclofen for spasticity of solely spinal origin. Antiepileptic medication permitted the continuation of intrathecal baclofen treatment in the three patients.

Indication, efficiency and complications of intrathecal pump supported baclofen treatment in spinal spasticity.

In 19 patients, who suffered from severe spinal spasticity of different etiologies and did not respond sufficiently to oral antispastic therapy, intrathecal Baclofen test boli were administered. In 11 patients a DAD (Drug Administration Device) [SynchroMedR Model 8611 H, Medtronic Inc. Minneapolis, USA] was implanted. Catheter dislocation or torsion was the most common complication to be observed in these 11 patients. Long term intrathecal Baclofen application was effective in all patients, as reducing spasticity, flexor spasms and spasm induced pain. In some cases the motor performance ameliorated.

Long-term intrathecal baclofen treatment in supraspinal spasticity.

Baclofen, a derivate of gamma-amino butyric acid (GABA), is known to be a useful drug in spasticity treatment. To achieve a good therapeutic response higher oral dosages have to be administered related with central side effects. Intrathecal application of Baclofen in microgram range dosages is proved to be effective in spinal spasticity. The efficiency of intrathecal Baclofen in patients suffering from supraspinal spasticity is discussed controversially. We report on 9 patients with long-term intrathecal Baclofen treatment, all of them responding well presenting a marked reduced muscle tone. In most cases an improvement of motor performance and in two cases improved bladder function was observed. The therapeutical dosages administered to patients with supraspinal spasticity exceed those administered to patients with spinal spasticity by approximately 100% without provoking central side effects. Despite the risks connected with this method it has to be considered as treatment of choice in cases of severe supraspinal spasticity.